Experimental colitis, induced in rats by intrarectal administration of trinitrobenzenesulfonic acid (TNB), results in a suppression of eating for 3 days. Because interleukin-1 (IL-1) is elevated within 24 h after TNB treatment, and because chronic administration of IL-1 leads to a pattern of anorexia similar to that seen after TNB, we evaluated the role of endogenous IL-1 in the anorexia observed in the TNB model. Human recombinant IL-1 receptor antagonist (rhIL-1ra) was administered chronically via osmotic minipump either peripherally or centrally after TNB treatment. Peripheral delivery of 40 micrograms/h rhIL-1ra significantly attenuated TNB-induced anorexia. However, 24 micrograms/h rhIL-1ra attenuated TNB-induced anorexia only when delivered centrally, not peripherally. These findings implicate central IL-1 receptors in the suppression of eating during acute experimental colitis but leave open a possible involvement of peripheral IL-1 receptors.